Brain shift and tissue deformation during surgery for intracranial lesions are the main actual limitations of neuro-navigation (NN), which currently relies mainly on preoperative imaging. Ultrasound ...(US), being a real-time imaging modality, is becoming progressively more widespread during neurosurgical procedures, but most neurosurgeons, trained on axial computed tomography (CT) and magnetic resonance imaging (MRI) slices, lack specific US training and have difficulties recognizing anatomic structures with the same confidence as in preoperative imaging. Therefore real-time intraoperative fusion imaging (FI) between preoperative imaging and intraoperative ultrasound (ioUS) for virtual navigation (VN) is highly desirable. We describe our procedure for real-time navigation during surgery for different cerebral lesions.
We performed fusion imaging with virtual navigation for patients undergoing surgery for brain lesion removal using an ultrasound-based real-time neuro-navigation system that fuses intraoperative cerebral ultrasound with preoperative MRI and simultaneously displays an MRI slice coplanar to an ioUS image.
58 patients underwent surgery at our institution for intracranial lesion removal with image guidance using a US system equipped with fusion imaging for neuro-navigation. In all cases the initial (external) registration error obtained by the corresponding anatomical landmark procedure was below 2 mm and the craniotomy was correctly placed. The transdural window gave satisfactory US image quality and the lesion was always detectable and measurable on both axes. Brain shift/deformation correction has been successfully employed in 42 cases to restore the co-registration during surgery. The accuracy of ioUS/MRI fusion/overlapping was confirmed intraoperatively under direct visualization of anatomic landmarks and the error was < 3 mm in all cases (100 %).
Neuro-navigation using intraoperative US integrated with preoperative MRI is reliable, accurate and user-friendly. Moreover, the adjustments are very helpful in correcting brain shift and tissue distortion. This integrated system allows true real-time feedback during surgery and is less expensive and time-consuming than other intraoperative imaging techniques, offering high precision and orientation.
Background
Synaptic Ras GTPase activating protein 1 (SYNGAP1)‐related non‐specific intellectual disability is a neurodevelopmental disorder caused by an insufficient level of SynGAP1 resulting in a ...dysfunction of neuronal synapses and presenting with a wide array of clinical phenotypes. Hematopoietic stem cell gene therapy has the potential to deliver therapeutic levels of functional SynGAP1 to affected neurons upon transduction of hematopoietic stem and progenitor cells with a lentiviral vector.
Methods
As a novel approach toward the treatment of SYNGAP1, we have generated a lentiviral vector expressing a modified form of SynGAP1 for transduction of human CD34+ hematopoietic stem and progenitor cells. The gene‐modified cells were then transplanted into adult immunodeficient SYNGAP1+/− heterozygous mice and evaluated for improvement of SYNGAP1‐related clinical phenotypes. Expression of SynGAP1 was also evaluated in the brain tissue of transplanted mice.
Results
In our proof‐of‐concept study, we have demonstrated significant improvement of SYNGAP1‐related phenotypes including an improvement in motor abilities observed in mice transplanted with the vector transduced cells because they displayed decreased hyperactivity in an open field assay and an increased latency to fall in a rotarod assay. An increased level of SynGAP1 was also detected in the brains of these mice.
Conclusions
These early‐stage results highlight the potential of this stem cell gene therapy approach as a treatment strategy for SYNGAP1.
A lentiviral vector encoding a modified form of SYNGAP1 is transduced into hematopoietic stem and progenitor cells (HSPCs). These gene‐modified HSPC will differentiate into mature immune system cells. A portion of these cells will migrate to the brain where they will reside as microglia. The gene‐modified microglia will express and secrete functional SynGAP1 protein to the affected neurons.
Clodronate induced uveitis Fietta, P; Manganelli, P; Lodigiani, L
Annals of the rheumatic diseases,
04/2003, Letnik:
62, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Bone densitometry dual energy x ray absorptiometry evaluation showed remarkably reduced mineral density in both vertebral and femoral neck sites (T score -4.3 and -4.08, respectively). Because the ...patient had had reflux oesophagitis, we treated her with 100 mg once a week of intramuscular (IM) clodronate, the only parenteral BP available for outpatients in our country. To our knowledge, ocular adverse manifestations have not hitherto been described for the non-N-BP clodronate. Because the BPs are successfully used in an increasingly broad range of diseases, we wish to report this observation, which suggests the need for a careful evaluation of ocular symptoms developing during treatment with any BP, independently of its chemical structure.
Eighty-seven subjects were examined by means of visual evoked potentials (VEPs) to evaluate the recovery time of the amplitude of the pattern VEP after photostress. Twenty-eight subjects were normal ...and 59 patients were affected by carotid occlusive disease, vascular retinopathies with and without macular involvement, and connective tissue diseases treated with antimalarial drugs. This examination method emphasizes visual dysfunction in a stage where ophthalmological changes are absent or minimal and therefore may be a useful test for the investigation of macular function.
Thirteen patients with carotid stenosis were studied by the authors by the measuring the Visual Evoked Potentials (VEPs) before and after thromboendarterectomy. This test of retinal function measures ...the recovery time of the amplitude of the major positive peak (P100) after photostress. When compared to that we observed in controls, we found, a significant increase of the P100 recovery time in patients suffering from carotid disease with severe stenosis. The method proved suitable for the functional evaluation of the vascular reconstruction of the carotid area, since four weeks after surgery a physiological recovery of the amplitude of VEP was observed. This method is proposed by the authors for the long-term functional evaluation of patients subjected to carotid thromboendarterectomy for tight stenosis of the carotid bifurcation.
Occupational asthma Imbriani, M; Lodigiani, L
Giornale italiano di medicina del lavoro
11, Številka:
5
Journal Article
Bronchial asthma has been defined as a state of airway obstruction of variable degree correlated casually with exposure to volatile dusts, gases, vapours or fumes in the working environment. In this ...review we considered the causes of occupational asthma, the diagnosis, the pattern of asthmatic reactions and their mechanism, the predisposing factors, the epidemiology, the prognosis and finally the cure and prevention (review article, 165 references).
Extrinsic Allergic Alveolitis (E.A.A.) is an immunological disorder caused by inhalation of various etiological agents (vegetable and animal dusts, fungi, organic simple chemicals) mostly present in ...work environment. Intensive and prolonged occupational exposure to antigens dimensionally able to reach peripheral airways, where they bring about their immunological effects, allows to consider hypersensitivity pneumonitis as a typical work-related disease. The wide range of pathological findings and evolution of E.A.A. often imply difficulty in diagnosis inspite of availability of diagnostic consolidated criteria. The integrated assessment of history and physical findings, radiological features, pulmonary functions tests, and specific and aspecific immunological data, often allows to make diagnostical conclusion without use of invasive methods (BAL and lung biopsy). In this note we refer two cases of E.A.A. occurred respectively in agricultural and industrial environment, whom etiological and evolutive features suggest an occupational pathogenesis. The first one is a typical "farmer's lung", the second one a hypersensitivity pneumonitis in a cheese washer. The diagnosis was performed by means of historical, clinical, radiological and pulmonary functional outcomes. In the first case specific serum precipitins against M. Faeni were present, in the second one the immunological pathogenesis of the pneumonitis was demonstrated by means of bronchial lavage cytological data and serum IgG dosage. In both cases the removal from specific antigen exposure and the prolonged steroid treatment induced symptomatological regression and complete recovery of functional tests.
Essentials Predicting recurrences may guide therapy after unprovoked venous thromboembolism (VTE). We evaluated the DASH score in 827 patients with unprovoked VTE to verify prediction accuracy. A ...DASH score ≤ 1 had a cumulative recurrence risk at 1 year of 3.6%, as predicted by the model. The DASH score performed better in younger (< 65 years old) subjects.
Background The DASH prediction model has been proposed as a guide to identify patients at low risk of recurrence of venous thromboembolism (VTE), but has never been validated in an independent cohort. Aims To validate the calibration and discrimination of the DASH prediction model, and to evaluate the DASH score in a predefined patient subgroup aged > 65 years. Methods Patients with a proximal unprovoked deep vein thrombosis (DVT) or pulmonary embolism (PE) who received a full course of vitamin K antagonist or direct oral anticoagulant (> 3 months) and had D-dimer measured after treatment withdrawal were eligible. The DASH score was computed on the basis of the D-dimer level after therapy withdrawal and personal characteristics at the time of the event. Recurrent VTE events were symptomatic proximal or distal DVT/PE, and were analyzed with a time-dependent analysis. Observed 12-month and 24-month recurrence rates were compared with recurrence rates predicted by the DASH model. Results We analyzed a total of 827 patients, of whom 100 (12.1%) had an objectively documented recurrence. As compared with the original DASH cohort, there was a greater proportion of subjects with a 'low-risk' (≤ 1) DASH score (66.3% versus 51.6%, P < 0.001). The slope of the observed versus expected cumulative incidence at 2 years was 0.71 (95% confidence interval 0.51-1.45). The c-statistic was lower for subjects aged > 65 years (0.54) than for younger subjects (0.72). Conclusions These results confirm the validity of DASH prediction model, particularly in young subjects. The recurrence risk in elderly patients (> 65 years) was, however, > 5% even in those with the lowest DASH scores.
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